共 22 条
Quebec platelet disorder is linked to the urokinase plasminogen activator gene (PLAU) and increases expression of the linked allele in megakaryocytes
被引:38
作者:

Diamandis, Maria
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机构: McMaster Univ, Hlth Sci Ctr, Dept Pathol & Mol Med, Hamilton, ON L8N 3Z5, Canada

Paterson, Andrew D.
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机构:
Hosp Sick Children, Dept Genet & Genome Biol, Toronto, ON M5G 1X8, Canada
Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON M5S 1A1, Canada
Univ Toronto, Inst Med Sci, Toronto, ON M5S 1A1, Canada McMaster Univ, Hlth Sci Ctr, Dept Pathol & Mol Med, Hamilton, ON L8N 3Z5, Canada

Rommens, Johanna M.
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机构:
Hosp Sick Children, Dept Genet & Genome Biol, Toronto, ON M5G 1X8, Canada
Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A1, Canada McMaster Univ, Hlth Sci Ctr, Dept Pathol & Mol Med, Hamilton, ON L8N 3Z5, Canada

Veljkovic, D. Kika
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机构: McMaster Univ, Hlth Sci Ctr, Dept Pathol & Mol Med, Hamilton, ON L8N 3Z5, Canada

Blavignac, Jessica
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机构: McMaster Univ, Hlth Sci Ctr, Dept Pathol & Mol Med, Hamilton, ON L8N 3Z5, Canada

Bulman, Dennis E.
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Ottawa Hlth Res Inst, Dept Regenerat Med, Ottawa, ON, Canada McMaster Univ, Hlth Sci Ctr, Dept Pathol & Mol Med, Hamilton, ON L8N 3Z5, Canada

Waye, John S.
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机构: McMaster Univ, Hlth Sci Ctr, Dept Pathol & Mol Med, Hamilton, ON L8N 3Z5, Canada

Derome, Francine
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机构:
Ctr Hosp Univ St Justine, Dept Hematol Oncol, Montreal, PQ, Canada McMaster Univ, Hlth Sci Ctr, Dept Pathol & Mol Med, Hamilton, ON L8N 3Z5, Canada

Rivard, Georges E.
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Ctr Hosp Univ St Justine, Dept Hematol Oncol, Montreal, PQ, Canada McMaster Univ, Hlth Sci Ctr, Dept Pathol & Mol Med, Hamilton, ON L8N 3Z5, Canada

Hayward, Catherine P. M.
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h-index: 0
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McMaster Univ, Hlth Sci Ctr, Dept Pathol & Mol Med, Hamilton, ON L8N 3Z5, Canada
McMaster Univ, Dept Med, Hamilton, ON L8N 3Z5, Canada McMaster Univ, Hlth Sci Ctr, Dept Pathol & Mol Med, Hamilton, ON L8N 3Z5, Canada
机构:
[1] McMaster Univ, Hlth Sci Ctr, Dept Pathol & Mol Med, Hamilton, ON L8N 3Z5, Canada
[2] Hosp Sick Children, Dept Genet & Genome Biol, Toronto, ON M5G 1X8, Canada
[3] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON M5S 1A1, Canada
[4] Univ Toronto, Inst Med Sci, Toronto, ON M5S 1A1, Canada
[5] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A1, Canada
[6] Ottawa Hlth Res Inst, Dept Regenerat Med, Ottawa, ON, Canada
[7] Ctr Hosp Univ St Justine, Dept Hematol Oncol, Montreal, PQ, Canada
[8] McMaster Univ, Dept Med, Hamilton, ON L8N 3Z5, Canada
来源:
关键词:
IDENTIFICATION;
TRANSLOCATION;
TRANSCRIPTION;
PATHOGENESIS;
MUTATION;
REGION;
D O I:
10.1182/blood-2008-08-175216
中图分类号:
R5 [内科学];
学科分类号:
1002 ;
100201 ;
摘要:
Quebec platelet disorder (QPD) is an autosomal dominant disorder with high penetrance that is associated with increased risks for bleeding. The hallmark of QPD is a gain-of-function defect in fibrinolysis due to increased platelet content of urokinase plasminogen activator (uPA) without systemic fibrinolysis. We hypothesized that increased expression of uPA by differentiating QPD megakaryocytes is linked to PLAU. Genetic marker analyses indicated that QPD was significantly linked to a 2-Mb region on chromosome 10q containing PLAU with a maximum multipoint logarithm of the odds (LOD) score of +11 between markers D10S1432 and D10S1136. Analysis of PLAU by sequencing and Southern blotting excluded mutations within PLAU and its known regulatory elements as the cause of QPD. Analyses of uPA mRNA indicated that QPD distinctly increased transcript levels of the linked PLAU allele with megakaryocyte differentiation. These findings implicate a mutation in an uncharacterized cis element near PLAU as the cause of QPD. ( Blood. 2009; 113: 1543-1546)
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页码:1543 / 1546
页数:4
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